4QKZ

X-ray structure of the catalytic domain of MMP-8 with the inhibitor ML115

Summary for 4QKZ

• Entry DOI: 10.2210/pdb4qkz/pdb
• Descriptor: Neutrophil collagenase, CALCIUM ION, ZINC ION, ... (6 entities in total)
• Functional Keywords: hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasmic granule: P22894
• Total number of polymer chains: 1
• Total formula weight: 18925.23

Authors

Pochetti, G.,Montanari, R.,Capelli, D.,Tortorella, P. (deposition date: 2014-06-10, release date: 2015-06-17, Last modification date: 2023-11-08)

Primary citation

Laghezza, A.,Piemontese, L.,Brunetti, L.,Caradonna, A.,Agamennone, M.,Di Pizio, A.,Pochetti, G.,Montanari, R.,Capelli, D.,Tauro, M.,Loiodice, F.,Tortorella, P.
Bone-Seeking Matrix Metalloproteinase Inhibitors for the Treatment of Skeletal Malignancy.
Pharmaceuticals, 13:-, 2020

PubMed Abstract: Matrix metalloproteinases (MMPs) are a family of enzymes involved at different stages of cancer progression and metastasis. We previously identified a novel class of bisphosphonic inhibitors, selective for MMPs crucial for bone remodeling, such as MMP-2. Due to the increasing relevance of specific MMPs at various stages of tumor malignancy, we focused on improving potency towards certain isoforms. Here, we tackled MMP-9 because of its confirmed role in tumor invasion, metastasis, angiogenesis, and immuno-response, making it an ideal target for cancer therapy. Using a computational analysis, we designed and characterized potent MMP-2/MMP-9 inhibitors. This is a promising approach to develop and clinically translate inhibitors that could be used in combination with standard care therapy for the treatment of skeletal malignancies.

PubMed: 32492898
DOI: 10.3390/ph13060113

Experimental method

X-RAY DIFFRACTION (1.2 Å)